The studies outlined in this proposal examine the role of the immune system on the initiation and perpetuation of acute and chronic alcohol-induced liver disease. The initial studies focus on the role of the cellular immune component (T-lymphocytes) in mediating cell damage. T-lymphocyte function will be examined by in vitro techniques. A pure T-lymphocyte population will be obtained from peripheral blood and from liver tissue for these studies. Both the sensitization phase (blast transformation) and the effector phase (cytotoxicity) of cell-mediated immunity as well as target cell specificity will be examined. Studies on the effect of serum inhibitory factors on T-lymphocyte function will also be performed. Attempts will be made to assess the presence and potency of a serum inhibitor (previously described by us) by measuring the percent inhibition of Con A-stimulated lymphocyte cytotoxicity obtained from normal controls when incubated in the presence of serum from patients with alcoholic liver disease. The role of B-lymphocytes and circulating serum factors in the initiation of a cytotoxic reaction against autologous and heterologous cells will also be examined. Cryoprotein immune complexes will be searched for in the sera of patients with alcohol-induced liver disease, particularly in alcoholic hepatitis. Attempts will be made to isolate, purify and characterize the components in the cryoproteins, and the presence and concentration of these complexes will be correlated with clinical disease. We hope to define the relationship of circulating cryoprotein immune complexes to complement sequence activation in alcoholic hepatitis, and to probe for etiological factors in immune complex formation by analyzing for the specific antigen components in the cryoprotein immune complexes.